Abstract

Colorectal cancer is the third leading cause of cancer-related deaths in the United States. Current treatment of this cancer generally employs surgical resection combined with chemotherapy using cytotoxic drugs and radiation therapy. Because this therapy is only moderately successful for late stage cancers, novel approaches to the treatment of colorectal cancer are required. Falcarindiol is a natural polyyne from medicinal plant Oplopanax horridus that has been widely used by indigenous people for a variety of diseases. We show that Falcarindiol can selectively kill colon cancer cells but not the normal colon cells. We further show that the observed cell death is mediated through the induction of Endoplasmic Reticulum (ER) stress. We further show that inhibition of ER stress significantly block Falcarindiol-induced colon cancer cell death while knockdown of GRP78, which sensitizes cells to ER stress induced cell death, significantly enhances Falcarindiol-induced cell killing. Interestingly, we find that Falcarindiol exhibits synergistic anticancer activity with 5-FU, a chemotherapeutic drug for colon cancer. These results suggest that Falcarindiol is potentially a valuable candidate that can be used to in the treatment of colon cancer either alone or in combination with current anti-colon cancer agent such as 5-FU. Key words: Falcarindiol; Colon cancer; ER Stress; Cell death.